Background: IgG4-Related Disease (IgG4-RD) is a multisystemic inflammatory disease characterized by fibrous swelling and IgG4+ plasma cells infiltration of affected organs. 18-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan is emerging as a promising imaging technique for diagnosis and staging of IgG4-RD, and for assessing treatment response. The relationship between FGD-PET findings and immunological perturbations occurring in IgG4-RD has never been evaluated. Objectives: To correlate the intensity and distribution of FDG-PET uptake with clinical and immunological parameters in patients with active untreated IgG4-RD. Methods: Patients with active, untreated, biopsy proven IgG4-RD were included in the study. Disease activity was assessed through clinical (IgG4-RD Responder Index (RI)) and immunological (erythrocyte sedimentation rate (ESR), Creactive protein (CRP), serum IgG4, and circulating plasmablasts) parameters. Plasmablasts, a recently characterized disease biomarker, were identified as CD19+CD20-CD27+CD38bright cells on flow cytometry. FDG-PET/CT was performed in all patients at diagnosis. Quantitative assessment of FDG uptake was measured using the mean Standardized Uptake Value corrected for the Partial Volume Effect (PVC-SUV) and with total lesion glycolysis (TLG). Lymph nodes < 1 cm of diameter were excluded from the analysis because of the risk of PVC-SUV over/under-estimation. In patients with multiorgan involvement, the IgG4-RD lesion with the highest PVC-SUV was selected to correlate FGD uptake with clinical and serological parameters. Results: We studied 19 patients (12 males, 7 females) with a mean age of 61 years (range, 30-78 years). Eleven (58%) patients had multiorgan IgG4-RD. Involved organs were: lymphnodes (8 patients), aorta (6 patients), pancreas (4 patients); lung, parotids and submandibolar glands (3 cases each), paranasal sinuses, palate, orbits, bones and lachrymal glands (2 cases each); meninges, thyroid, subcutaneous nodule and spleen (one case each). The median IgG4-RD RI was 6 (range 6-15; normal < 3). The median levels of ESR, CRP, serum IgG4 and plasmablasts at baseline were 30 mm/h (range 4-121 mm/h, normal <20 mm/h), 9,9 mg/L (range 0.0-48.0 mg/L; normal <6mg/L), 455 mg/dL (range 80-2100 mg/dL, normal <135 mg/dL), and 5365 cells/mL (range 130-40840 cells/mL, normal <650 cells/mL), respectively. The median PCV-SUV was 10.36 (range, 2.78-39.34). Significant positive correlation was found between PVC-SUV and circulating plasmablasts levels (r=.46, p=.004). No statistically significant correlation was found between either PVC-SUV or TLG and the values of CRP, ESR, serum IgG4 levels, and IgG4-RD RI at baseline (p>.05). . Conclusions: We demonstrate for the first time a positive correlation between circulating plasmablasts and inflammatory activity of IgG4-RD lesions as assessed by PVC-SUV on FDG-PET. Inflammatory markers, serum IgG4 levels, and IgG4-RD RI do not appear to correlate with metabolic activity in IgG4-RD lesions. Our results further strengthen the utility of circulating plasmablasts as a biomarker of IgG4-RD activity.
INFLAMMATORY ACTIVITY OF IgG4-RELATED DISEASE LESIONS ASSESSED BY QUANTITATIVE POSITRON EMISSION TOMOGRAPHY CORRELATES WITH CIRCULATING PLASMABLASTS LEVELS
M. Lanzillotta;DELLA TORRE E
2016-01-01
Abstract
Background: IgG4-Related Disease (IgG4-RD) is a multisystemic inflammatory disease characterized by fibrous swelling and IgG4+ plasma cells infiltration of affected organs. 18-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan is emerging as a promising imaging technique for diagnosis and staging of IgG4-RD, and for assessing treatment response. The relationship between FGD-PET findings and immunological perturbations occurring in IgG4-RD has never been evaluated. Objectives: To correlate the intensity and distribution of FDG-PET uptake with clinical and immunological parameters in patients with active untreated IgG4-RD. Methods: Patients with active, untreated, biopsy proven IgG4-RD were included in the study. Disease activity was assessed through clinical (IgG4-RD Responder Index (RI)) and immunological (erythrocyte sedimentation rate (ESR), Creactive protein (CRP), serum IgG4, and circulating plasmablasts) parameters. Plasmablasts, a recently characterized disease biomarker, were identified as CD19+CD20-CD27+CD38bright cells on flow cytometry. FDG-PET/CT was performed in all patients at diagnosis. Quantitative assessment of FDG uptake was measured using the mean Standardized Uptake Value corrected for the Partial Volume Effect (PVC-SUV) and with total lesion glycolysis (TLG). Lymph nodes < 1 cm of diameter were excluded from the analysis because of the risk of PVC-SUV over/under-estimation. In patients with multiorgan involvement, the IgG4-RD lesion with the highest PVC-SUV was selected to correlate FGD uptake with clinical and serological parameters. Results: We studied 19 patients (12 males, 7 females) with a mean age of 61 years (range, 30-78 years). Eleven (58%) patients had multiorgan IgG4-RD. Involved organs were: lymphnodes (8 patients), aorta (6 patients), pancreas (4 patients); lung, parotids and submandibolar glands (3 cases each), paranasal sinuses, palate, orbits, bones and lachrymal glands (2 cases each); meninges, thyroid, subcutaneous nodule and spleen (one case each). The median IgG4-RD RI was 6 (range 6-15; normal < 3). The median levels of ESR, CRP, serum IgG4 and plasmablasts at baseline were 30 mm/h (range 4-121 mm/h, normal <20 mm/h), 9,9 mg/L (range 0.0-48.0 mg/L; normal <6mg/L), 455 mg/dL (range 80-2100 mg/dL, normal <135 mg/dL), and 5365 cells/mL (range 130-40840 cells/mL, normal <650 cells/mL), respectively. The median PCV-SUV was 10.36 (range, 2.78-39.34). Significant positive correlation was found between PVC-SUV and circulating plasmablasts levels (r=.46, p=.004). No statistically significant correlation was found between either PVC-SUV or TLG and the values of CRP, ESR, serum IgG4 levels, and IgG4-RD RI at baseline (p>.05). . Conclusions: We demonstrate for the first time a positive correlation between circulating plasmablasts and inflammatory activity of IgG4-RD lesions as assessed by PVC-SUV on FDG-PET. Inflammatory markers, serum IgG4 levels, and IgG4-RD RI do not appear to correlate with metabolic activity in IgG4-RD lesions. Our results further strengthen the utility of circulating plasmablasts as a biomarker of IgG4-RD activity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
